Human rhinoviruses (HRVs) represent the single most important etiological agents of the common cold (Arruda et al., J. Clin. Microbiol. 35:2864-2868 (1997); Couch, “Rhinoviruses.” In: Fields, B. N., Knipe, D. M. (Eds.), Virology. Raven Press, New York, 607-629 (1990); Turner, Antivir. Res. 49(1):1-14 (2001)). HRVs causing about one-third of the outbreaks of the common cold are represented by about 100 serotypes, the convalescent sera from patients infected with which are not fully cross-neutralizing. Although HRV-induced upper respiratory illness is often mild and self-limiting, the socioeconomic impact caused by missed work or school is enormous and the degree of inappropriate antibiotic use is significant. It has been estimated that upper respiratory disease accounts for at least 25 million absences from work and 23 million absences of school annually in the United States (Anzueto et al., Chest 123(5):1664-1672 (2003); Rotbart, Antivir. Res. 53:83-98 (2002)).
There is increasing evidence of a link between HRV infection and more serious medical complications. For example, HRV-induced colds are the important predisposing factors to acute otitis media and sinusitis, and are major factors in the induction of exacerbations of asthma in adults and children. HRV infections are also associated with lower respiratory tract syndromes in individuals with cystic fibrosis, bronchitis, and other underlying respiratory disorders (Gern, Pediatr. Infect. Dis. J. 23:S78-S86 (2004); Anzueto et al., Chest 123(5):1664-1672 (2003); Gem et al., Clin. Microbiol. Rev. 12(1):9-18 (1999); Pitkaranta et al., J. Clin. Microbiol. 35:1791-1793 (1997); Pitkaranta et al., Pediatrics 102:291-295 (1998); Rotbart, Antivir. Res. 53:83-98 (2002)).
To date, no effective antiviral therapies have been approved for either the prevention or treatment of diseases caused by HRV infection. Thus, there exists a significant unmet medical need to find agents that can prevent HRV infection, shorten the duration of HRV-induced illness, lessen the severity of symptoms, minimize secondary bacterial infections and exacerbations of underlying disease, and reduce virus transmission. A prophylactic HRV vaccine should be protective against a wide variety of serotypes to reduce the number of HRV infections and their clinical impact.
Attempts to make HRV vaccines based on synthetic peptides corresponding to conserved regions of structural proteins alone (McCray et al., Nature 329:736-738 (1987)) or as a part of biological fusions (Brown et al., Vaccine 9:595-601 (1991); Francis et al., Proc. Natl. Acad. Sci. U.S.A. 87:2545-2549 (1990)) have had limited success, due to low immunogenicity of chosen peptides, which may be partially explained by their low exposure on the virus surface (limited access to antibodies) or conformational constraints.
The present invention overcomes these limitations and features a vaccine that elicits a protective serotype cross-reactive neutralizing antibody response to prevent and treat HRV infection.